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Aims The aim of this study was to investigate the effect of subchronic administration of agomelatine on energy metabolism, oxidative stress markers and antioxidant defense in the brains of rats. Methods The animals received daily intraperitoneal injections of agomelatine (10, 30 or 50 mg/kg) or saline for 14 days. The prefrontal cortex, cerebellum, hippocampus, striatum and posterior cortex were analyzed. Results The findings showed that complex I was activated in the prefrontal cortex, cerebellum and striatum and inhibited in the posterior cortex at the 10-mg/kg dose, and inhibited in all brain areas analyzed at the 30-mg/kg and 50-mg/kg doses. Complex II was activated in the posterior cortex at the 50-mg/kg dose. Complex IV was inhibited in the striatum and posterior cortex at the 10-mg/kg dose, inhibited in the striatum at the 30-mg/kg dose and activated in the hippocampus at the 50-mg/kg dose. Creatine kinase activity was inhibited in the striatum at the 10-mg/kg and 30-mg/kg doses. Lipid peroxidation and protein carbonylation levels were not changed after the administration of agomelatine. Superoxide dismutase activity was increased in the striatum at the 10-mg/kg dose, and catalase activity was inhibited in the cerebellum at the 10-mg/kg dose and increased in the posterior cortex at the 30-mg/kg dose. Conclusions Our results are consistent with other studies showing that some antidepressants may influence brain energy metabolism and oxidative stress parameters and expand knowledge about the effects of agomelatine in biochemical parameters in the brains of rats.

The pathophysiology of gastritis involves an imbalance between gastric acid attack and mucosal defence. In addition, the gastric mucosal injury results in adenosine triphosphate (ATP) depletion leading to mitochondrial dysfunction. Several studies have shown the association of mitochondrial disorders with gastrointestinal dysfunction. In the present study, we investigated the activity of mitochondrial respiratory chain complexes activity in the stomach of rats with gastritis induced by indomethacin (IDM) and treated with omeprazole (OM), N-acetylcysteine (NAC) and the gastrin-releasing peptide receptor (GRPR) antagonist RC-3095. Adult male Wistar rats were pre-treated for 7 days with OM, NAC, RC-3095, combination of OM plus RC-3095, OM plus NAC and water (control). The animals were then submitted to fasting for 24 hr; IDM was administered. The rats were killed 6 hr later, and the stomachs were used for evaluation of macroscopic damage and respiratory chain activity. Our results showed that complex I and IV activities were not affected by administration of IDM. On the other hand, complex II and III activities were inhibited. In addition, OM plus RC-3095 and OM plus NAC did not reverse complex II activity inhibition. However, the complex III activity inhibition was reversed only with the combined use of OM plus RC-3095 and OM plus NAC. Our results are in agreement with previous studies indicating mitochondrial dysfunction in the pathophysiology of gastrointestinal tract disease and we suggest that GRPR antagonism might be a novel therapeutic strategy in gastritis.

In this study we investigated energy metabolism in the mdx mouse brain.To this end, prefrontal cortex, cerebellum, hippocampus, striatum, and cortex were analyzed. There was a decrease in Complex I but not in Complex II activity in all structures. There was an increase in Complex III activity in striatum and a decrease in Complex IV activity in prefrontal cortex and striatum. Mitochondrial creatine kinase activity was increased in hippocampus, prefrontal cortex, cortex, and striatum. Our results indicate that there is energy metabolism dysfunction in the mdx mouse brain.